Birth weight and head circumference discordance and outcome in preterms: results from the EPIPAGE-2 cohort.

OBJECTIVE: To determine whether the relative measurement of birth weight (BW) and head circumference (HC) in preterm infants is associated with neurological outcomes. METHODS: The EPIPAGE-2 Study included 3473 infants born before 32 weeks' gestation, classified based on their Z-score of BW and HC on the Fenton curves as concordant (≤1 SD apart) or discordant (>1 SD difference). We defined four mutually exclusive categories: discordant smaller BW (sBW) with BW-1SD and concordant small measurement (CsM) with BW and HC concordant and both ≤-1SD. Neurological outcomes at 5.5 years were evaluated with standard tests. RESULTS: 2592 (74.8%) preterm neonates were categorised as CM, 258 (7.4%) CsM, 378 (10.9%) sHC and 239 (6.9%) sBW. Compared with the CM children, those born with CsM had significantly higher risks of cognitive deficiency (adjusted OR (aOR) 1.3, 95% CI (1.0 to 2.0)), developmental coordination disorders (aOR 2.6 (1.5 to 4.4)) and need for special school services (aOR 2.3 (1.5 to 3.7)). Those born with sBW had significantly lower risk of cognitive deficiency (aOR 0.6 (0.4 to 0.9)) and the sHC group significantly higher risk of developmental coordination disorders (aOR 1.8 (1.0 to 3.2)). CONCLUSIONS: The relative discordance of these preterm infants' BW and HC was associated with their neurological outcomes. It merits further exploration as an indirect indicator of development. TRIAL REGISTRATION NUMBER: NCT03078439.

Associations of screen use with cognitive development in early childhood: the ELFE birth cohort.

BACKGROUND: The associations of screen use with children's cognition are not well evidenced and recent, large, longitudinal studies are needed. We aimed to assess the associations between screen use and cognitive development in the French nationwide birth cohort. METHODS: Time and context of screen use were reported by parents at ages 2, 3.5 and 5.5. Vocabulary, non-verbal reasoning and general cognitive development were assessed with the MacArthur-Bates Communicative Development Inventory (MB) at age 2, the Picture Similarities subtest from the British Ability Scales (PS) at age 3.5 and the Child Development Inventory (CDI) at ages 3.5 and 5.5. Outcome variables were age-adjusted and standardized (mean = 100, SD = 15). Multiple imputations were performed among children (N = 13,763) with ≥1 screen use information and ≥1 cognitive measures. Cross-sectional and longitudinal associations between screen use and cognitive development were assessed by linear regression models adjusted for sociodemographic and birth factors related to the family and children, and children's lifestyle factors competing with screen use. Baseline cognitive scores were further considered in longitudinal analysis. RESULTS: TV-on during family meals at age 2, not screen time, was associated with lower MB scores at age 2 (ß [95% CI] = -1.67 [-2.21, -1.13]) and CDI scores at age 3.5 (-0.82 [-1.31, -0.33]). In cross-sectional analysis, screen time was negatively associated with CDI scores at ages 3.5 (-0.67 [-0.94, -0.40]) and 5.5 (-0.47 [-0.77, -0.16]), and, in contrast, was positively associated with PS scores (0.39 [0.07, 0.71]) at age 3.5. Screen time at age 3.5 years was not associated with CDI scores at age 5.5 years. CONCLUSIONS: Our study found weak associations of screen use with cognition after controlling for sociodemographic and children's birth factors and lifestyle confounders, and suggests that the context of screen use matters, not solely screen time, in children's cognitive development.

Cord blood leptin level and a common variant of its receptor as determinants of the BMI trajectory: The EDEN mother-child cohort.

BACKGROUND: Cord blood leptin is an indicator of neonatal fat mass and could shape postnatal adiposity trajectories. Investigating genetic polymorphisms of the leptin receptor gene (LEPR) could help understand the mechanisms involved. OBJECTIVES: We aimed to investigate the association of cord blood leptin level and the LEPR rs9436303 polymorphism, with body mass index (BMI) at adiposity peak (AP) and age at adiposity rebound (AR). METHODS: In the EDEN cohort, BMI at AP and age at AR were estimated with polynomial mixed models, for 1713 and 1415 children, respectively. Multivariable linear regression models allowed for examining the associations of cord blood leptin level and LEPR rs9436303 genotype with BMI at AP and age at AR adjusted for potential confounders including birth size groups. We also tested interactions between cord blood leptin level and rs9436303 genotype. RESULTS: Increased leptin level was associated with reduced BMI at AP and early age at AR (comparing the highest quintile of leptin level to the others). Rs9436303 G-allele carriage was associated with increased BMI at AP and later age at AR but did not modulate the association with leptin level. CONCLUSION: These results illustrate the role of early life body composition and the intrauterine environment in the programming of adiposity in childhood.

Pediatric Outpatient Prescriptions in Countries With Advanced Economies in the 21st Century: A Systematic Review.

Importance: An international comparison of pediatric outpatient prescriptions (POPs) is pivotal to investigate inadequate practices at the national scale and guide corrective actions. Objective: To compare annual POP prevalence among Organisation for Economic Co-operation and Development (OECD) member countries. Evidence Review: Two independent reviewers systematically searched PubMed, Embase, and institutes of public health or drug agency websites for studies published since 2000 and reporting POP prevalence (expressed as number of patients aged <20 years with ≥1 POP per 1000 pediatric patients per year) in OECD member countries or large geographic areas within them. Risk of bias was assessed for exhaustiveness and representativeness. Prevalence ratios (PRs) were used to compare the highest and lowest POP prevalence among countries overall, by levels of Anatomical Therapeutic Chemical (ATC) classification for the overall pediatric population, and by age group (ie, ages <5-6 vs ≥5-6 years), stratifying on prescription-only drug (POD) status. Findings: Among 11 studies performed on 3 regional and 8 national medicoadministrative databases in 11 countries, 35 552 550 pediatric patients were included. The overall risk of bias was low (10 studies were representative [90.9%], and the prevalence denominator included nonusers of health care for 9 studies [81.8%]). Prevalence of 1 or more POP per year ranged from 480 to 857 pediatric patients per 1000 in Sweden and France, respectively (PR, 1.8 [95% CI, 1.8-1.8]). Overall, among 8 studies reporting ATC level 1 drugs, Denmark had the lowest POP prevalence (eg, systemic hormonal preparations: 9 pediatric patients per 1000 per year) and France the highest (eg, systemic hormonal preparation: 216 pediatric patients per 1000 per year). Among 8 studies reporting ATC level 2 drugs for PODs, the PR between France and Denmark was 108.2 (95% CI, 108.2-108.2) for systemic corticosteroids and 2.1 (95% CI, 2.1-2.1) for drugs for obstructive airway disease. The PR for antibiotics was 3.4 (95% CI, 3.4-3.4) between New Zealand and Sweden. For pediatric patients aged 5 to 6 years or older, the PR for sex hormones was 2.1 (95% CI, 2.1-2.1) between Denmark and France. Among 7 studies reporting ATC level 5 drugs, the prevalence of the 10 most prevalent PODs was less than 100 pediatric patients per 1000 per year in Scandinavian countries and the Netherlands and less than 300 pediatric patients per 1000 per year in France and New Zealand. Conclusions and Relevance: This study found large between-country variations in POPs, which may suggest substantial inappropriate prescriptions. The findings may suggest guidance for educational campaigns and regulatory decisions in some OECD member countries.

LC-PUFA enrichment in infant formula and neurodevelopment up to age 3.5 years in the French nationwide ELFE birth cohort.

PURPOSE: For decades, consistent associations between breastfeeding and children's neurodevelopment have been attributed to breastmilk content in long-chain polyunsaturated fatty acids (LC-PUFAs). However, the beneficial effect of LC-PUFA enrichment of infant formula on neurodevelopment remains controversial. This study examined the association of LC-PUFA enrichment of infant formulas with neurodevelopment up to age 3.5 years. METHODS: Analyses were based on 9372 children from the French nationwide ELFE birth cohort. Monthly from 2 to 10 months, parents declared their infant's feeding mode, including breastfeeding and the name of the infant formula, which allowed for identifying formulas enriched in arachidonic (ARA), eicosapentaenoic (EPA) and/or docosahexaenoic (DHA) acids. Neurodevelopment was assessed at age 1 and 3.5 years with the Child Development Inventory (CDI-1 and CDI-3.5); at 2 years with the MacArthur-Bates Communicative Development Inventories (MB-2); and at 3.5 years with the Picture Similarities subtest of the British Ability Scale (BAS-3.5). Associations were assessed by linear regression adjusted for any breastfeeding duration and main confounding factors, including socioeconomic characteristics. RESULTS: One-third of formula-fed infants consumed LC-PUFA-enriched formulas. Most of these formulas were enriched in both DHA and ARA, and about 10% of infants consumed formula further enriched in EPA. LC-PUFA enrichment of infant formula was not associated with neurodevelopmental scores at age 1 (CDI-1, - 0.16 [- 0.39, 0.07]), age 2 (MB-2, 0.78 [- 0.33, 1.89]), or age 3.5 (CDI-3.5, - 0.05 [- 0.27, 0.17]; BAS-3.5, - 0.93 [- 2.85, 0.98]). CONCLUSION: In the ELFE study, LC-PUFA enrichment of infant formula was not associated with neurodevelopmental scores up to 3.5 years.

Pediatric Prescriptions of Proton Pump Inhibitors in France (2009-2019): A Time-Series Analysis of Trends and Practice Guidelines Impact.

OBJECTIVE: To describe the ambulatory proton pump inhibitor (PPI) prescription in French children, its trends, and the impact of French (2014) and international (2018) clinical guidelines. STUDY DESIGN: We described PPI prescription rates based on national dispensation data in French children (IQVIA's Xponent database, 2009-2019). Using a segmented linear regression, we assessed the impact of clinical guidelines on PPI prescription rates. Analyses were performed for the overall pediatric population and by age subgroups (infants <2 years old, children 2-11 years old, adolescents 12-17 years old). RESULTS: During the study period, 8 060 288 pediatric PPI prescriptions were filled, with a mean PPI prescription rate of 52.5 per 1000 inhabitants per year. Between 2009 and 2019, the PPI prescription rate increased by 41% in the overall pediatric population (+110% in infants). The PPI prescription rate showed seasonal patterns with peaks in winter. After the release of French guidelines, significant decreases in trends of prescription rates occurred overall (change in trend -0.28, 95% CI -0.34;-0.23) and across all age groups. In infants, this change in trend was not sufficient to reverse the PPI prescription rate that was still increasing over time. In children, the PPI prescription rate slightly decreased and in adolescents, it was stable. After the release of international guidelines, a significant decrease in trend occurred in adolescents only (change in trend -0.26, 95% CI -0.47; -0.04). CONCLUSIONS: The pediatric PPI prescription rate in France was high, displayed a major increase over the last decade, mainly among infants, and was modestly affected by clinical guidelines.

Serious Infections in Children Born to Mothers With Inflammatory Bowel Disease With In Utero Exposure to Thiopurines and Anti-Tumor Necrosis Factor.

BACKGROUND & AIMS: We aimed to compare the risk of serious infections in children with in utero exposure to thiopurines and/or anti-tumor necrosis factor (TNF) born to mothers with inflammatory bowel disease (IBD). METHODS: Using the French national health database, which covers 99% of the French population (around 66,000,000 people), we identified live births among women with IBD in France between 2010 and 2018. The risks of serious infections in children during the first 5 years of life were compared according to treatment exposures during pregnancy using propensity score-weighted marginal Cox models. RESULTS: A total of 26,561 children were included: 3392 were exposed to thiopurine monotherapy, 3399 to anti-TNF monotherapy, 816 to combination therapy, and 18,954 were not exposed to any of these drugs. The risks of serious infections during the first year of life among children exposed to thiopurine monotherapy (adjusted hazard ratio [aHR], 0.94; 95% confidence interval [CI], 0.83-1.07) and anti-TNF monotherapy (aHR, 1.10; 95% CI, 0.95-1.27) were similar to those of unexposed children; a higher risk was observed in children exposed to combination therapy (aHR, 1.36; 95% CI, 1.04-1.79). The highest increased risks were observed for nervous system infections and viral infections. The risk of serious infections during the second to fifth years of life was not associated with IBD treatments. CONCLUSIONS: In children born to mothers with IBD, in utero exposure to thiopurine and anti-TNF monotherapies do not increase the risk of serious infections during the first 5 years of life. Combination therapy is associated with an increased risk of serious infections during the first year of life.

Head circumference from birth to five years in France: New national reference charts and comparison to WHO standards.

BACKGROUND: The monitoring of head circumference (HC) is essential to early detect any conditions affecting its growth in early childhood. A positive secular trend and regional specificities in HC suggested the need to provide updated national HC reference growth charts. METHODS: We extracted all growth data collected from 42 primary-care physicians from across the French metropolitan territory who used the same electronic medical-records software. We selected HC measurements up to age five years for all children who were born after 1990 with birth weight > 2500 g. We derived new HC growth charts by using Generalized Additive Models for Location, Scale and Shape, then externally validated them until 30 months of age by comparison with the national population-based Étude Longitudinale Française depuis l'Enfance (ELFE) birth cohort and compared them to previous French and WHO growth charts. FINDINGS: With 973,869 HC measurements from 157,762 children, new calibrated HC growth charts from birth to age five years were generated. The new HC growth charts showed good external fit by comparison with the ELFE birth cohort. As compared with the new HC growth charts, the previous French and WHO growth charts mean HC z-scores were, respectively, -0.4 and -0.6 SD for girls and -0.2 and -0.6 SD for boys. INTERPRETATION: We produced and validated national calibrated HC growth charts by using a novel big-data approach applied to data routinely collected in clinical practice. Comparison with previous French and WHO growth charts confirmed a positive secular trend since the 1960s and regional specificities. FUNDING: The French Ministry of Health; Laboratoires Guigoz-General Pediatrics section of the French Society of Pediatrics-Paediatric Epidemiological Research Group; the French Association of Ambulatory Pediatrics; and educational grant from the Regional Health Agency of Ile-de-France.

Paediatric outpatient prescriptions in France between 2010 and 2019: A nationwide population-based study: Paediatric outpatient prescriptions in France, 2010 to 2019.

BACKGROUND: Paediatric outpatient prescription (POP) monitoring is pivotal to identify inadequate prescriptions and optimize drug use. We aimed at describing recent trends in POPs in France. METHODS: All reimbursed dispensations of outpatient prescribed drugs (excluding vaccines) were prospectively collected for the paediatric population (<18 years old) in the French national health database in 2010-2011 and 2018-2019 (mean 117,356,938/year). POP prevalence (proportion of children receiving ≥1 drug prescriptions/year) was calculated by age groups and compared by prevalence rate ratios (PRRs). Given the large sample size, 95% confidence intervals of POP prevalences and PRRs did not differ from estimates. FINDINGS: Among the 14,510,023 children resident in France in 2018-2019, mean POP prevalence was 857‰ children. Most prescribed therapeutic classes were analgesics (643‰), antibiotics (405‰), nasal corticosteroids (328‰), nonsteroidal anti-inflammatory drugs (NSAIDs) (244‰), antihistamines (246‰) and systemic corticosteroids (210‰). POPs decreased with age from 976‰ for infants to 782‰ for adolescents. Children <6 years old were notably more exposed to inhaled corticosteroids (PRR=3.06), non-penicillin beta-lactam antibacterial agents (PRR=3.05) and systemic corticosteroids (PRR=2.11) than older ones. The POP prevalence was slightly higher (PRR=1.04) during 2018-2019 than 2010-2011, with marked increases for anti-emetics (PRR=1.84), vitamin D (PRR=1.49), proton pump inhibitors (PRR=1.42), systemic contraceptives (PRR=1.24) and nasal corticosteroids (PRR=1.21) and decreases for propulsive/prokinetic agents (PRR=0.09), NSAIDs (PRR=0.73) and systemic antibiotics (PRR=0.88). INTERPRETATION: POP remained highly prevalent in France throughout the 2010s, especially for children <6 years old, with only a few improvements for selected therapeutic classes. These findings should prompt clinical guidance campaigns and/or regulatory policies. FUNDING: Internal funding.

Early postnatal growth and subsequent neurodevelopment in children delivered at term: The ELFE cohort study.

BACKGROUND: Despite the limited evidence, accelerated early postnatal growth (EPG) is commonly believed to benefit neurodevelopment for term-born infants, especially those small for gestational age. OBJECTIVES: To investigate the existence of critical time windows in the association of EPG with neurodevelopment, considering birth size groups. STUDY DESIGN: In the French ELFE birth cohort, 12,854 term-born neonates were classified as small, appropriate or large for gestational age (SGA, AGA, LGA, respectively). Parents reported their child's development by using the Child Development Inventory (CDI-score) at age 12 months and the MacArthur-Bates Development Inventory (MAB-score; 100 score units) assessing language ability at age 24 months. Predictions of individual weight, body mass index (BMI), length, and head circumference (HC) from birth to age 24 months were obtained from repeated measurements fitted with the Jenss-Bayley mixed-effects model. For each infant, conditional gains (CG) in these growth parameters were generated at four-time points (3, 6, 12 and 24 months) representing specific variations in growth parameters during 0-3, 3-6, 6-12, 12-24 months, independent of previous measures. Using multivariable linear regression models, we provided the estimate differences of the neurodevelopmental scores according to variation of each growth parameter CG, by birth size group. RESULTS: For SGA infants, the MAB-score differed by 5.8 (95% confidence interval [CI] -0.2, 11.8), 6.7 (95% CI -0.1, 13.3), and 9.7 (95% CI 1.9, 17.5) score units when CG in BMI, weight, and HC at 3 months varied from -2 to 1 standard deviation, respectively. For all infants, MAB-score was linearly and positively associated with length conditional gains at 12 months, with stronger magnitude for SGA infants. Results for the CDI-score were overall consistent with those for MAB-score. CONCLUSIONS: For term-born SGA infants, moderate catch-up in HC, BMI and weight within the first 3 months of life may benefit later neurodevelopment, which could guide clinicians to monitor EPG.

Mandatory Infant Vaccinations in France During the COVID-19 Pandemic in 2020.

Objectives: To describe changes in the dispensation of 11 mandatory vaccines to infants in France during the COVID-19 pandemic in 2020, considering the priming doses and boosters separately. Methods: With data from the French national health database, all dispensations of priming doses and boosters of 11 mandatory vaccines [penta/hexavalent, measles mumps rubella (MMR), meningococcal conjugate type-C (Men-C-C), 13-valent pneumococcal conjugate (PCV13)] for infants ≤24 months old were aggregated by 4-week periods in 2020. Expected counts in 2020 were estimated according to counts in 2019 weighted by a ratio considering the level of vaccine dispensation before the pandemic onset in 2020. Relative differences (RDs) and their 95% confidence intervals (CIs) were computed to compare the observed and expected counts during the first and second lockdown and the period in between. Results: During the first 4 weeks of the first lockdown, as compared with the expected numbers, the observed priming dose counts substantially decreased [RD: from -5.7% (95% CI -6.1; -5.2) for penta/hexavalent to -25.2% (95% CI -25.6; -24.8) for MMR], as did the booster counts [RD: from -15.3% (95% CI -15.9; -14.7) for penta/hexavalent to -20.7% (95% CI -21.3; -20.2) for Men-C-C]. Counts for priming doses and boosters remained slightly below the expected numbers after the lockdown. During 2020, MMR priming doses and the Men-C-C booster had the greatest shortfalls (N = 84,893 and 72,500, respectively). Conclusions: This study provides evidence of a lack of vaccination catch-up after the first lockdown and a persistent shortfall in infant vaccination after the first 10 months of the COVID-19 pandemic in France, especially for the MMR priming doses and Men-C-C booster.

Does cord blood leptin level mediate the association between neonatal body size and postnatal growth? Results from the EDEN mother-child cohort study.

Background: Leptin is potentially involved in the correction of early postnatal growth of infants having deviated from their genetic trajectory in utero.Aim: To analyse the potential mediating role of cord blood leptin level in the association between neonatal anthropometry and early postnatal growth in the mother-child EDEN cohort.Subjects and methods: We included term newborns with information on leptin, birth weight and length, and weight and length SD-score changes over the first 2 months. The Baron and Kenny method was used to quantify the mediation contribution of leptin in the association between neonatal anthropometry and postnatal growth, considering several confounders. Analyses were stratified to consider sexual dimorphism.Results: A 1 SD higher birth weight was associated with a lower 2-months weight variation of 0.27 (0.18; 0.36) SD and a 0.16 (0.06; 0.26) SD, in boys and girls, respectively. Leptin explained 20% and 25% of these associations, respectively. Leptin did not mediate the association between birth length and birth-to-2 months length variation.Conclusion: Our results suggest that cord blood leptin may not be involved in the negative association between birth length and postnatal length growth but may play a modest mediating role in early postnatal catch-up or catch-down in weight.

Maternal immigrant status and signs of neurodevelopmental problems in early childhood: The French representative ELFE birth cohort.

A growing body of evidence suggests that children of immigrants may have increased risks of neurodevelopmental disorders. However, evidence based on parent report and on very young children is lacking. We therefore investigated the association between maternal immigrant status and early signs of neurodevelopmental problems in a population-based sample of 2-year-old children using standardized parent-report instruments. We used data from the French representative Étude Longitudinale Française depuis l'Enfance birth cohort, initiated in 2011. The study sample included 9,900 children of nonimmigrant French, 1,403 children of second, and 1,171 children of first generation immigrant women followed-up to age 2 years. Neurodevelopment was assessed using the Modified Checklist for Autism in Toddlers (M-CHAT) and an adaptation of the MacArthur-Bates Communicative Development Inventories (MB-CDI). In fully adjusted linear regression models, maternal immigrant status was associated with M-CHAT scores, with stronger associations in children of first (ß-coefficient: 0.19; 95% CI 0.08-0.29) than second generation immigrants (0.09; 0.01-0.17). This association was especially strong among children of first generation immigrant mothers native of North Africa (vs. nonimmigrant French: 0.33; 0.16-0.49) and French-speaking Sub-Saharan Africa (0.26; 0.07-0.45). MB-CDI scores were lowest among children of first generation immigrant mothers, particularly from mostly non-francophone regions. Children of first generation immigrant mothers were most likely to have simultaneously low MB-CDI and high M-CHAT scores. Our findings suggest that maternal immigrant status is associated with early signs of neurodevelopmental difficulties, with strong variations according to maternal region of origin. Further research is necessary to test whether these associations persist and to determine the underlying mechanisms. Autism Res 2019, 12: 1845-1859. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We asked immigrant and nonimmigrant mothers in France about early signs of neurodevelopmental problems in their 2-year-old children. Overall, we found that children of immigrants may be at higher risk of showing these early warning signs, as compared to children of nonimmigrants. This is in line with previous studies, which were based on doctors' diagnoses at later ages. However, our results differed depending on the mothers' regions of origin. We found the highest risks in children of first generation immigrants from North and French-speaking Sub-Saharan Africa, who also seemed especially at risk of neurodevelopmental problems combined with low language development.

Developmental trajectories of motor skills during the preschool period.

Children with developmental coordination disorder also manifest difficulties in non-motor domains (attentional, emotional, behavioral and socialization skills). Longitudinal studies can help disentangle the complex relationships between the development of motor skills and other cognitive domains. This study aims to examine the contribution of early cognitive factors to changes in motor skills during the preschool period. Children (N = 1144) from the EDEN mother-child cohort were assessed for motor skills with the Copy Design task (NEPSY battery) and the parent-rated Ages and Stages Questionnaire (fine and gross motor skills scores) at ages 3 and 5-6 years. At 3 years, language skills were evaluated using tests from the NEPSY and ELOLA batteries. Emotional problems, conduct problems, inattention and hyperactivity symptoms, peer relationships and pro-social behavior were assessed with the Strengths and Difficulties Questionnaire (SDQ) also at 3 years. Linear and logistic regression models were performed to examine whether positive and negative changes in motor skills between 3 and 5-6 years are associated with specific cognitive skills at 3 years, while adjusting for a broad range of pre- and postnatal environmental factors. In the linear regression model, the SDQ Inattention symptoms score at 3 years was associated with negative changes in motor skills (standardized ß = - 0.09, SD = 0.03, p value = 0.007) and language skills at 3 years were associated with positive changes in motor skills (standardized ß = 0.05, SD = 0.02, p value = 0.041) during the preschool period. In logistic regression models, the SDQ Inattention symptoms score at 3 years was associated with a higher likelihood of a declining trajectory of motor skills (OR [95% CI] = 1.37 [1.02-1.84]). A higher language skills score at 3 years was associated with an increased likelihood of a resilient trajectory (1.67 [1.17-2.39]). This study provides a better understanding of the natural history of developmental coordination delays by identifying cognitive factors that predict changes in motor skills between the ages of 3 and 5-6 years.

Sex differences in psychomotor development during the preschool period: A longitudinal study of the effects of environmental factors and of emotional, behavioral, and social functioning.

We sought to determine the extent to which sex differences in psychomotor development during the preschool period can be explained by differential exposure to environmental factors and/or differences in emotional, behavioral, or social functioning. Children from the EDEN mother-child cohort were assessed for language, gross motor, and fine motor skills at 2, 3, and 5-6 years of age using parental questionnaires and neuropsychological tests. Structural equation models examining the associations between sex and language, gross motor, and fine motor skills at 2, 3, and 5-6 years were performed while adjusting for a broad range of pre- and postnatal environmental factors as well as emotional, behavioral and socialization difficulties. Girls (n = 492) showed better fine motor skills than boys (n = 563) at 2 years (Cohen's d = 0.67 in the fully adjusted models), at 3 years (d = 0.72), and to a lesser extent at 5-6 years (d = 0.29). Girls also showed better language skills at 2 years (d = 0.36) and 3 years (d = 0.37) but not at 5-6 years (d = 0.04). We found no significant differences between girls and boys in gross motor skills at 2, 3, or 5-6 years. Similar results were found in the models unadjusted and adjusted for pre- and postnatal environmental factors as well as emotional, behavioral, and socialization difficulties. Our findings are consistent with the idea that sex differences in fine motor and language skills at 2 and 3 years of age are not explained by differential exposure to environmental factors or by sex differences in emotional, behavioral, or social functioning.

Early postnatal growth and neurodevelopment in children born moderately preterm or small for gestational age at term: A systematic review.

BACKGROUND: Clinicians' interest in the long-term effects of early postnatal growth (EPG) is growing. There is compelling evidence linking rapid EPG with later cardiovascular risk, but its neurodevelopmental benefits still remain hypothetical in individuals born moderately preterm (MP) or small for gestational at term (SGAT). METHODS: The objective was to perform a systematic review of the relationship between EPG before age 3 years and neurodevelopmental outcome for individuals born MP (32-36 weeks' gestational age) or SGAT. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, 3 independent investigators searched for articles published on this topic in the Web of Science, EMBASE and PubMed from database inception to July 1, 2017. A detailed quality scale was used to evaluate articles. RESULTS: We selected 19 articles relying on 12 distinct study populations; 7 articles from 3 study populations were considered at moderate or high quality. The lack of standardisation of growth analysis methods prevented performing a meta-analysis. Overall, EPG was positively associated with neurodevelopmental outcome, especially Intelligence Quotient (IQ) when available. In this relationship, the first 6 months of life might be a critical period. Analysis of the few articles investigating the shape of the relationships revealed a non-linear association, with a plateau for IQ with higher weight gain, which suggests a possible ceiling effect. CONCLUSIONS: A positive association was generally found between EPG and neurodevelopmental outcome for individuals born MP or SGAT. Strategies for future epidemiological studies are suggested to improve the characterisation of this relationship.

Rapid Early Growth May Modulate the Association Between Birth Weight and Blood Pressure at 5 Years in the EDEN Cohort Study.

Physiological evidence suggests that birth weight (BW) and postnatal growth affect blood pressure (BP) level, independently or in interaction. Their respective roles are difficult to disentangle in epidemiological studies, however, especially when adjusting for final weight. We assessed the portion of the effect of BW on BP at 5 years that was not attributable to postnatal growth and investigated potential interactions between BW and postnatal growth velocity at different time points in the EDEN mother-child study. Collecting a median of 19 weight measurements for each of the 1119 children who completed follow-up enabled us to model instantaneous growth velocity at any age. After computing a BP SD-score at 5 years, adjusted for age, sex, current body mass index, and height, we used multiple linear regression to study its association with age- and sex-specific BW z score, adjusting for several maternal and pregnancy risk factors. We tested interactions between BW categories (small-, appropriate-, and large-for-gestational-age) and weight growth velocities at different ages. The BW z score was negatively and significantly correlated with the systolic BP SD-score at the age of 5 years (r=-0.07, P=0.02). Interactions were found between BW categories and weight growth velocities from 1 to 4 months (P from 0.002 to 0.08) but not at older ages; specifically, children born small for gestational age with a fast weight growth velocity in their first few months of life had the highest absolute systolic BP and SD score values at 5 years. They may need monitoring for cardiovascular risks.